Increasing number of vectors implicated in transmission

Q. Please review bartonellosis in animals and humans.

A. Dr. Edward B. Breitschwerdt at the 2006 American College of Veterinary Internal Medical Forum in Louisville, Ky., lectured on "Bartonellosis: Legal and Medical Implications for Veterinarians." Here are some relevant points from his presentation:

The genus Bartonella is currently comprised of at least 20 species and subspecies of vector-transmitted, fastidious, gram-negative bacteria that are highly adapted to one or more mammalian reservoir hosts. Recent reports have provided additional evidence supporting intra-erythrocytic and endothelial localization of Bartonella, which provides a potentially unique strategy for bacterial persistence.

Based on recent research observations, the clinical and diagnostic challenges posed by Bartonella transmission in nature may be much more complex than is currently appreciated in either human or veterinary medicine.

As reviewed in several publications, numerous domestic and wild animals, including bovine, canine, feline, human and rodent species can serve as chronically infected reservoir hosts for various Bartonella species. In addition to the large number of documented reservoir hosts, an increasing number of arthropod vectors, including biting flies, fleas, keds, lice, sandflies and potentially ticks have been implicated in the transmission of Bartonella species.

In general, persistent bacteremia in a reservoir host does not induce obvious signs of disease or pathology. However, when a Bartonella species is transmitted from a reservoir host (a seemingly well-adapted association) to a non-reservoir host (a poorly adapted association) by a cat scratch, an animal bite or by an arthropod vector, infection can induce a diverse spectrum of clinical and pathological abnormalities.

Manifestations in humans

In people, Bartonella-induced disease manifestations can include fever of unknown origin, endocarditis, lymphadenopathy (cat-scratch disease), granulomatous hepatitis, encephalitis, and bacillary angiomatosis and peliosis hepatis, particularly in immunocompromised individuals.

Although not previously reported, our research group recently described putative bite transmission of Bartonella quintana from a feral barn cat to a woman followed by a second and unrelated episode of bite transmission of B. vinsonii berkhoffii from her pet dog. Dog and cat bites are a frequent cause of emergency-room presentations in the United States and may well represent an under-recognized source of Bartonella transmission to people.

These and other recent findings emphasize the potential environmental complexity associated with putative Bartonella bite transmission.

To date, four Bartonella species have been isolated from cats, including B. henselae, B. clarridgeiae, B. bovis and B. koehlerae. Based on well-documented publications or recent research abstracts, it is possible that all four of these Bartonella species can be zoonotic pathogens. In addition to the frequent cat-scratch transmission of B. henselae (cat-scratch disease) and potentially B. clarridgeiae, there is increasing evidence that cats may be involved in the transmission of B. quintana to people. Recently, B. quintana DNA was amplified from the dental pulp of a cat and from cat fleas (Ctenocephalides felis) in France.

Prior to these reports, a laboratory has also described two middle-aged female patients that had chronic peripheral or mediastinal adenomegaly, respectively, who were infected with B quintana. Both women had close contact with cats. Central nervous system infection with B. quintana was documented in two males from the southeastern United States, one of whom had experienced numerous scratches on the upper extremities by a kitten several weeks prior to the onset of seizures.

B. quintana also was implicated as the cause of seizures in an 11-year-old boy who had been scratched by a kitten a few weeks prior to admission. This child had no prior history of fever or lymphadenopathy. When tested by the Centers for Disease Control (CDC) in Atlanta, both B. quintana and B. henselae reciprocal titers were 2048, but only B. quintana DNA was detected in a serum sample. The historical failure to isolate B. quintana from cats may reflect infrequent bacteremia or perhaps a lack of sensitivity to currently available culture techniques.

The extent to which dogs might contribute to the transmission of a Bartonella species to a human being by way of a bite or scratch is currently unknown. Canines, including dogs, foxes and coyotes, can serve as reservoirs for Bartonella vinsonii (berkhoffii). Recently, there have been four distinct genotypes of B. vinsonii (berkhoffii), with types I, II and IV found in dogs, types I and II in coyotes, and type III in gray foxes.

To date, B. vinsonii (berkhoffii) has been isolated from only one reported case of human endocarditis in Europe. Currently, there are no other reports suggesting B. vinsonii berkhoffii transmission from dogs to people via a scratch or bite. However, during the past year, both the CDC and the Intracellular Pathogens Laboratory at North Carolina State University have isolated B. vinsonii (berkhoffii) from human blood samples. The route of transmission has not been clearly established in these individuals because they all have a history of extensive animal and arthropod contact.

Canine transmission

There are only a few reports in the world literature implicating dogs in the transmission of B. henselae to people. The extent to which dogs can serve as a reservoir host for B. henselae has not been established, but B. henselae seroreactivity in healthy and sick dogs in the southeastern United States is much higher than B. vinsonii (berkhoffii) seroprevalences in comparable dog populations. Similar to people, dogs can develop endocarditis and presumably other serious disease manifestations when infected with non-reservoir Bartonella species, including B. clarridgeiae, B. quintana and B. washoensis.

Other than two dogs with B. quintana endocarditis, one from North Carolina and the other from New Zealand, and one dog each with B. clarridgeiae and B. washoensis endocarditis (both from California), there are no other reports of infection with these non-reservoir Bartonella species in dogs, making bite transmission of these species from a dog to a human less likely.

Bartonella species have been isolated from numerous wild terrestrial animals, including deer, fox, lions, rabbits, raccoons and numerous rodent species. Recently, we reported the first detection of a Bartonella species from the blood of a cetacean, the harbor porpoise (Phocoena phocoena). Of potential importance, this represents the first evidence of B. henselae infection in a non-terrestrial animal.

Disease in marine mammals

In recent years, a series of emerging or re-emerging infection diseases with serious epizootic and/or zoonotic potential had been described in marine mammals. These infectious threats, which include morbilliviruses, brucellosis, toxoplasmosis, sarcocystosis, papillomavirus and West Nile virus, seem linked to anthropogenic factors. As was the case for brucellosis, which was recognized as a marine-mammal emerging disease in 1994, bartonellosis may prove to be an important emerging marine-mammal infectious disease in the future. Currently, the geographic distribution, the mode of transmission, the reservoir potential and the pathogenicity of blood-borne Bartonella species in porpoises is yet to be determined.

Because conventional microbiological techniques lack sensitivity, bartonellosis is usually diagnosed by PCR amplification of organism-specific DNA sequences and/or through serological testing. Recently, the development of a more sensitive isolation approach, using BAPGM (Bartonella alpha Proteobacteria growth medium), followed by real-time PCR, has greatly facilitated the molecular detection or isolation of Bartonella species from the blood of sick or healthy animals, including humans. Obviously, the relative sensitivity of the diagnostic methods used to detect Bartonella species infection greatly influences an investigator's ability to establish disease causation. The use of recently optimized microbiological techniques has facilitated the recognition of blood-borne Bartonella spp. infections in dogs, horses, humans and porpoises in our laboratory.

Based on the annual increase in publications related to Bartonella infections in animals and people during the past decade, it is obvious that members of this genus are gaining increased international scrutiny by the medical and scientific communities. When examining data generated in specific populations of naturally exposed healthy or sick animals, it is important to recognize the exceptional evolutionary adaptation of these micro-organisms, which are able to induce persistent blood-borne infections in both animals and people. This adaptation complicates efforts to define causation in association with intravascular Bartonella infection.

Veterinarians' exposure

Animals function as a blood reservoir for various Bartonella species, a process that facilitates a continued transmission cycle via arthropod, animal bites or scratches. Animal contact, which in many instances occurs to a wide spectrum of domestic and wild-animal species, is an obvious consequence of the daily activities of veterinarians, veterinary technicians, animal-health researchers, ranchers, wildlife biologists and many other individuals in our society. During the past year, B. henselae or B. vinsonii (berkhoffii) infection in blood samples from people with extensive arthropod and animal contact has been documented. The potential clinical relevance of detecting Bartonella species in the blood of people with occupational animal contact is yet to be determined.

Despite frequent occupational exposure to animals, it is important to acknowledge that most veterinary professionals, ranchers and wildlife biologists participate in a diversity of outdoor recreational and occupational activities that also increase the opportunity for Bartonella transmission by biting arthropods.

Veterinarians are responsible for the medical care and general well-being of all animal species on this planet, except for Homo sapiens. In regard to zoonotic disease transmission, veterinarians play a pivotal role in the public health infrastructure of the United States. Additional prospective studies are necessary to characterize the risk of human Bartonella infection following a cat or dog bite and whether these infections are always self-limiting.

Although part of the natural evolutionary history of Bartonella and mammals, the legal implications of Bartonella transmission from pets to people in our society may create complications as well as opportunities for the veterinary profession.

Johnny D. Hoskins

Research abstract

Bartonella spp. antigen recognition patterns in cats with and without fever.

M.R. Lappin; J.R. Hawley; E.B. Breitschwerdt. (Colorado State University, Fort Collins, CO; North Carolina State University, Raleigh, NC.)

Bartonella spp. infections are common in cats. Some cats with Bartonella spp. DNA in blood or antibodies in serum are clinically ill and have fever leading to the hypothesis that the organisms may be associated with fever of unknown origin. In addition, it has been hypothesized that western blot immunoassay (WB) results can be used to predict Bartonella spp. bacteremia.

The objective of this study was to use WB to determine whether Bartonella spp. antigen recognition patterns exist that correlate to the presence of fever or presence of Bartonella spp. DNA in blood.

An IgG heavy, chain-specific WB using blood-agar-grown B. henselae as the antigen source was optimized using sera collected over time from experimentally inoculated cats. Nine immunodominant antigens were selected by analysis of the pre-infection and post-infection results. Matched serum and blood samples from client-owned cats with (n = 20) or without fever (n = 19) that resided in high flea prevalence states were selected for analysis, using the optimized WB and a previously published conventional PCR assay. Results of the serum WB were considered positive if any two or more of the nine antigens were recognized and were greater than a predetermined appropriate density. Results of the PCR assay on blood were considered positive if an amplicon of the appropriate size was detected.

Fisher's exact test was used to compare between groups for some parameters; significance was defined as p < 0.05.

WB results were positive in 10 of 20 cats (50 percent) with fever and six of 19 cats (31.6 percent) without fever; differences between groups were not significant (p = 0.1998). PCR assay results were positive in five of 20 cats (25 percent) with fever and one of 19 cats (5.3 percent) of cats without fever; differences between groups were not significant (p = 0.1022). Of 16 WB positive cats, three were PCR positive (percentage concordance = 59 percent). All three PCR positive but WB negative samples were from acutely ill, febrile cats.

Three or more antigens were recognized by five of 10 (50 percent) WB positive cats with fever and five of six (83.3 percent) WB positive cats without fever. Antigens with the apparent molecular masses of 48, 57, 62, 69 and 82 kD were each recognized by at least four cats but there was no antigen recognition pattern that was specifically detected in cats with or without fever.

We conclude that determination of Bartonella spp. antigen recognition patterns in this sample set could not be used to predict which cats had fever associated with Bartonella spp. infection. In addition, presence of antibodies detected by WB did not reliably correlate with the presence or absence of Bartonella spp. DNA in blood and so should not be used to predict the infection status of individual cats. Lastly, in peracute infections, Bartonella spp. serum antibody test results can be falsely negative.

Dr. Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail: jdhoskins@mindspring.com